The compounds of the above-mentioned formula (I) are highly selective and long-acting antagonists of α2-adrenoceptors and they have a good peroral bioavailability. The compounds are especially valuable in the treatment of cognitive disorders. Compounds of formula (I) have been described in patent publication EP 0 618 906 B1. Specific examples of such compounds are 4-(2-ethyl-5-fluoroindan-2-yl)-1H-imidazole and 4-(5-fluoroindan-2-yl)-1H-imidazole.
The above-mentioned publication EP 0 618 906 B1 also discloses methods of preparing compounds of formula (I). Said methods relate to various ways of modifying the substituents in the benzene moiety of the indan ring system. There is no disclosure of a total synthesis, which would lead to the desired compounds in good yield.
Publication EP 0 310 745 B1 discloses a process for preparing compounds of formula (I), wherein the last step of the process comprises the use of formamide for the formation of the imidazole ring. The use of formamide, however, requires severe reaction conditions, which should be avoided in connection with industrial production in large scale.
Although the individual steps of the process according to the present invention are known as such (see e.g. EP 0 146 228 B1), it has now surprisingly been found that compounds of formula (I) can be prepared, also in large scale, in very good yields by using the synthesis route described below.